In vitro Antibacterial Activity of 7-Substituted-6-Fluoroquinolone and 7-Substituted-6,8-Difluoroquinolone Derivatives

Abstract

Background: Fluoroquinolones are widely prescribed synthetic antimicrobial agents. Quinolones act by converting their targets, gyrase and topoisomerase IV, into toxic enzymes that fragment the bacterial chromosome; the irreversible DNA damage eventually causes the killing of bacteria. Thorough knowledge of the structure-activity relationship of quinolones is essential for the development of new drugs with improved activity against resistant strains. Methods: The compounds were screened for their antibacterial activity against 4 representing strains using the Kirby-Bauer disk diffusion method. Minimal inhibitory concentration (MIC) was determined by measuring the diameter of the inhibition zone using concentrations between 250 and 0.004 μg/mL. Results: MIC of derivatives 2, 3, and 4 showed potent antimicrobial activity against gram-positive and gram-negative bacteria. The effective concentrations were 0.860 μg/mL or lower. MIC for compounds 5-11 were between 120 and 515 μg/mL against Escherichia coli and Staphylococcus aureus, and substituted hydrazinoquinolones 7-10 showed poor antibacterial activity against gram-positive and gram-negative bacteria compared with other quinolones. Conclusion: Compounds obtained by modifications on C-7 of norfloxacin with the acetylated piperazinyl, halogen atoms, and substituted hydrazinyl showed good in vitro activity - some even better than the original compound.

Fluoroquinolones’ Biological Activities against Laboratory Microbes and Cancer Cell Lines

“…Norfloxacin inhibitory activity against a panel of Gram-negative bacterial type, and on the same bacterial strain is noted to be varied. For instance, norfloxacin in vitro antibacterial activity reported by Pardeshi et al against E. coli ATCC 25922 varied from that reported by Leyva-Ramos et al (MIC ranged from < 0.094 µM [ 24 ]−117.433 µM [ 45 ]). Moreover, norfloxacin and ciprofloxacin MIC against different P. aeruginosa strains ranged from 1.002 µM [ 1 ]−1565.773 µM [ 45 ] and <0.091 [ 62 ] µM−150.901 µM [ 42 ], respectively, in different studies.…”

“…For instance, norfloxacin in vitro antibacterial activity reported by Pardeshi et al against E. coli ATCC 25922 varied from that reported by Leyva-Ramos et al (MIC ranged from < 0.094 µM [ 24 ]−117.433 µM [ 45 ]). Moreover, norfloxacin and ciprofloxacin MIC against different P. aeruginosa strains ranged from 1.002 µM [ 1 ]−1565.773 µM [ 45 ] and <0.091 [ 62 ] µM−150.901 µM [ 42 ], respectively, in different studies. On the contrary, ciprofloxacin MIC against a panel of Gram–negative pathogens looks more consistent ( A. haemolyticus ATCC 19002 (MIC 0.755 µM) [ 62 ], A. baumannii ATCC17961 (MIC 0.24 µM) [ 58 ], A. calcoacetious ATCC 19606 (MIC 1.509 µM) [ 55 ], and C. freundii ATCC 43864 (MIC 1.38 µM) [ 51 ].…”

“…As reported, norfloxacin was used as a positive control in the pipeline publications, including norfloxacin derivatives synthesis. Norfloxacin MIC against Gram-positive is presented in Table 3 [ 1 , 23 , 24 , 26 , 28 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ]. In brief, norfloxacin inhibitory activity against a panel of Gram-positive bacteria regardless of the strain varied relatively.…”

“…For example, norfloxacin in vitro antibacterial activity reported by Mentese et al against E. faecalis ATCC 29212 varied from that reported by Seliem et al (MIC ranged from <0.128 µM [ 46 ]−100.207 µM [ 47 ]). Similarly, norfloxacin MIC against S. aureus ATCC 25923 ranged from <0.128 µM [ 46 ]–156.170 µM [ 45 ] in the above-mentioned two different studies.…”

Antimicrobial Activity of Galangin and Its Effects on Murein Hydrolases of Vancomycin-Intermediate Staphylococcus aureus (VISA) Strain Mu50

“…Staphylococcus aureus has long been recognized as a major cause of hospital-acquired infections [1,2]. Over the last decade, methicillin-resistant S. aureus (MRSA) strains have become endemic in hospitals worldwide, and the frequency of MRSA isolation continues to be high [3,4,5].…”